Progress in the Development of Broadly Reactive Norovirus Therapeutics

Discovered over five decades ago, norovirus is frequently reported as the leading cause of outbreaks of acute gastroenteritis. No vaccines or antivirals are currently available. We further analyzed two of our leading norovirus inhibitors that either indirectly or directly obstructed norovirus from binding to histo-blood group antigen receptors. Using X-ray crystallography, we showed that both inhibitors engage highly conserved capsid residues amongst genetically diverse noroviruses. The indirect inhibitor, a modified Fc-linked Nanobody, showed improved binding affinity and neutralization capacity compared with the native Nanobody. More strikingly, we showed that the direct inhibitor, a chewable prebiotic tablet containing human milk oligosaccharide 2’-fucosyllactose, worked as an inhibitor for a leading norovirus. These new discoveries are expected to promote the development of effective norovirus treatments.